The subject of the invention is nucleotide sequences coding for a urease such as that naturally expressed in Campylobacter pylori and its biological uses, in particular for the detection of C. pylori in man or in the environment.
C. pylori is a Gram negative bacterium found at present exclusively at the surface of the mucous membranes of the antral part of the stomach in man, and more particularly around the lesions and craters of gastric and duodenal ulcers. 25% of the population are carriers of C. pylori: 8% have an ulcerous disease, 9% suffer from non-ulcerous dyspepsia and 8% are asymptomatic carriers.
All of the C. pylori isolated and described up to the present possess the three following properties:
The bacteria produce a urease endowed with high activity.
They adhere very tightly to epithelial cells of the gastric mucosa, this property being reflected in vitro in a very tight adhesion to Hela cells.
The C. pylori produce and release an enzyme possessing a proteolytic activity leading to the degradation of mucus and, hence, to a weakening of the barrier which naturally protects the gastric mucosa.
The detection of C. pylori in situ in man and in the environment and the study of its pathogenicity--it is considered as being responsible for active gastritis in man--is, however, confronted with difficulty with respect to the culture of this organism.
Its growth is very slow (6 to 7 days on blood agar medium) and it must be grown under microaerophilic conditions, the oxygen of the air being toxic.
The search for agents to detect this bacterium has led the investigators to identify the genes in C. pylori responsible for the production of urease.
The determination of the nucleotide sequence of an intragenic fragment has made available a tool which can be used as detection probe for the specific identification of the C. pylori.